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661.
Bunkoczi G Salah E Filippakopoulos P Fedorov O Müller S Sobott F Parker SA Zhang H Min W Turk BE Knapp S 《Structure (London, England : 1993)》2007,15(10):1215-1226
Apoptosis signal-regulating kinase 1 (ASK1) plays an essential role in stress and immune response and has been linked to the development of several diseases. Here, we present the structure of the human ASK1 catalytic domain in complex with staurosporine. Analytical ultracentrifugation (AUC) and crystallographic analysis showed that ASK1 forms a tight dimer (K(d) approximately 0.2 microM) interacting in a head-to-tail fashion. We found that the ASK1 phosphorylation motifs differ from known ASK1 phosphorylation sites but correspond well to autophosphorylation sites identified by mass spectrometry. Reporter gene assays showed that all three identified in vitro autophosphorylation sites (Thr813, Thr838, Thr842) regulate ASK1 signaling, but site-directed mutants showed catalytic activities similar to wild-type ASK1, suggesting a regulatory mechanism independent of ASK1 kinase activity. The determined high-resolution structure of ASK1 and identified ATP mimetic inhibitors will provide a first starting point for the further development of selective inhibitors. 相似文献
662.
Haifeng Li Anton Valouev David C Schwartz Michael S Waterman Lei M Li 《Journal of computational biology》2007,14(3):255-266
Optical mapping is an integrated system for the analysis of single DNA molecules. It constructs restriction maps (noted as "optical map" ) from individual DNA molecules presented on surfaces after they are imaged by fluorescence microscopy. Because restriction digestion and fluorochrome staining are performed after molecules are mounted, resulting restriction fragments retain their order. Maps of fragment sizes and order are constructed by image processing techniques employing integrated fluorescence intensity measurements. Such analysis, in place of molecular length measurements, obviates need for uniformly elongated molecules, but requires samples containing small fluorescent reference molecules for accurate sizing. Although robust in practice, elimination of internal reference molecules would reduce errors and extend single molecule analysis to other platforms. In this paper, we introduce a new approach that does not use reference molecules for direct estimation of restriction fragment sizes, by the exploitation of the quantiles associated with their expected distribution. We show that this approach is comparable to the current reference-based method as evaluated by map alignment techniques in terms of the rate of placement of optical maps to published sequence. 相似文献
663.
Effects of different pH and carbon sources on pullulan production, UDP-glucose level and pullulan-related synthases activity inAureobasidium pullulans Y68 were examined. It was found that more pullulan was produced when the yeast strain was grown in the medium with initial pH 7.0 than when it was grown in the same medium with constant pH 6.0. The results also show that higher pullulan yield was obtained when the cells were grown in the medium containing glucose than when they were cultivated in the medium supplementing other carbon sources. Our results demonstrate that the more pullulan was synthesized, the less UDP-glucose was left in the cells ofA. pullulans Y68. However, it was observed that more pullulan was synthesized; the cells had higher pullulan-related synthase activity. Therefore, high pullulan yield was related to low UDP-glucose level and high pullulan-related synthases activity inAureobasidium pullulans Y68. 相似文献
664.
Xiong Yuping Liang Hanzhi Yan Haifeng Guo Beiyi Niu Meiyun Chen Shuangyan Jian Shuguang Ren Hai Zhang Xinhua Li Yuan Zeng Songjun Wu Kunlin Zheng Feng Teixeira da Silva Jaime A. Ma Guohua 《Plant Cell, Tissue and Organ Culture》2019,139(3):531-546
Plant Cell, Tissue and Organ Culture (PCTOC) - To investigate the mechanisms underlying salt tolerance, physiological parameters of six halophyte species [Vitex rotundifolia L., Clerodendrum inerme... 相似文献
665.
Huang Zhi Lian Yajun Chen Yuan Li Shuang Zhang Haifeng Xie Nanchang Zheng Yake Wu Shouyi Wang Yuhan Cheng Wenchao Zhang Qiaoman Wang Chengze Shi Yinping Xie Na 《Neurochemical research》2019,44(5):1262-1268
Neurochemical Research - Botulinum neurotoxins (BoNTs) block the release of a series of neurotransmitters, which are pivotal for neuron action. Intrahippocampal administration of BoNTs inhibits... 相似文献
666.
Haifeng Wang Xiande Yang Caili Zhao Peng George Wang Xin Wang 《Bioorganic & medicinal chemistry》2019,27(8):1639-1645
A new series of glucose-conjugated Pt(IV) complexes that target tumor-specific glucose transporters (GLUTs) was designed, synthesized, and evaluated for their anticancer activities. All six compounds, namely, A1-A6, exhibited increased cytotoxicity that were almost six fold higher than that of oxaliplatin to MCF-7 cells. These Pt(IV) complexes can be reduced to release Pt(II) complexes and cause the death of tumor cells. Simultaneously, the glycosylated Pt(IV) complexes (30.21–91.33?μM) showed lower cytotoxicity that normal LO2 cells compared with cisplatin (5.25?μM) and oxaliplatin (8.34?μM). The intervention of phlorizin as a GLUTs inhibitor increased the IC50 value of the glycosylated Pt(IV) complexes, thereby indicating the potential GLUT transportability. The introduction of glucose moiety to Pt(IV) complexes can effectively enhance the Pt cellular uptake and DNA platination. Results suggested glucose-conjugated Pt(IV) complexes had potential for further study as new anticancer agents. 相似文献
667.
DELLA蛋白是GA信号传导途径的核心作用元件,属于GRAS核转录调节因子家族。该研究以‘魏可’葡萄品种为试材,通过基因克隆、启动子分析、染色体定位、基因蛋白结构及系统进化分析,鉴定VvRGL1和VvRGL2精确序列,预测其潜在功能,并采用qRT-PCR技术检测VvRGL基因应答GA在果皮、果肉及种子(区)的时空表达特征。结果表明:(1)VvRGL1及VvRGL2的染色体定位为Chr14和Chr7,开放阅读框(ORF)为2 007bp和1 815bp,编码氨基酸数量为668和604个;二者均含有GRAS保守结构域,但却不具备DELLA结构域,属于GRAS转录因子大家族成员,而不属于DELLA亚家族;基因结构分析表明,VvRGL1的DNA序列有1个内含子,2个外显子,而VvRGL2的DNA序列无内含子,有1个外显子,基因结构高度保守;进化分析表明,VvRGL1与拟南芥和柑桔的亲缘关系较近,而VvRGL2与草莓和杨树的亲缘关系较近。(2)2个基因的启动子均含有响应赤霉素和胚乳发育相关的作用元件,表明它们可能参与响应GA信号传导和种子胚乳发育过程。(3)qRT-PCR结果显示,外源GA处理均不同程度降低了2个基因在葡萄果皮和种子区的表达,但却上调了其在幼果期果肉中的表达,表明在果皮与种子(区)中,GA可能通过抑制葡萄VvRGL1/RGL2基因的表达参与调控葡萄无核果实的发育。本研究结果为进一步阐明VvRGL在赤霉素信号传导及葡萄无核果实发育机理中的作用机制提供重要依据。 相似文献
668.
Jiangtao Feng Haifeng He Yuan Zhou Meng Cai Hao Peng Honglin Liu Lei Liu Lingling Feng Hongwu He 《Bioorganic & medicinal chemistry》2019,27(24):115159
Harmful cyanobacteria bloom (HCB) has occurred frequently in recent years and it is urgent to develop novel algicides to deal with this problem. In this paper, a series of novel thiamin diphosphate (ThDP) analogs 5a?5g were designed and synthesized targeting cyanobacterial pyruvate dehydrogenase complex E1 (Cy-PDHc E1). Our results showed that compounds 5a?5g have higher inhibitory activities against Cy-PDHc E1 (IC50 9.56–3.48 µM) and higher inhibitory activities against two model cyanobacteria strains Synechocystis sp PCC6803 (EC50 2.03–1.58 µM) and Microcystis aeruginosa FACHB905 (EC50 1.86–0.95 µM). Especially, compound 5b displayed highest inhibitory activities (IC50 = 3.48 µM) against Cy-PDHc E1 and powerful inhibitory activities against cyanobacteria Synechocystis sp PCC6803 (EC50 = 1.58 µM) and Microcystis aeruginosa FACHB905 (EC50 = 1.04 µM). Moreover, the inhibitory activities of compound 5b were even higher than those of copper sulfate (EC50 = 2.02 and 1.71 µM separately) which has been widely used as algicide against cyanobacteria PCC6803 and FACHB905. The more important was that compound 5b display much higher inhibitory selectivity between Cy-PDHc E1 (Inhibitory rate 97.4%) and porcine PDHc E1 (Inhibitory rate 11.8%) under the same concentration (100 μM). The inhibition kinetic experiment and molecular docking research showed that compound 5b can inhibit Cy-PDHc E1 by occupying the ThDP-binding pocket and then blocking Cy-PDHc E1 bound to ThDP as competitive inhibitor. The imagines of SEM and TEM showed that cellular microstructures were heavily destroyed under compound 5b stress. Our results demonstrated compound 5b could be taken as a potential lead compound targeting Cy-PDHc E1 to obtain environment-friendly algicide for harmful cyanobacterial blooms control. 相似文献
669.
670.